Epileptogenic spikes and seizures but not high voltage spindles are induced by local frontal cortical application of gamma-hydroxybutyrate.

Combining the methods of microdialysis and EEG recording, we have examined the effect of unilaterally, intracortically applied gamma-hydroxybutyrate (GHB) on frontal cortical EEG activity in freely moving rats. GHB, a natural endogenous GABA metabolite, is known to induce rhythmic spike and wave activity, resembling generalized petit mal epilepsy. Without GHB, spontaneous high voltage spindles (HVS, 6-9 Hz) were observed during awake and immobile behavior in most of the animals (HVS rats), while others never had any HVS. In those both groups of animals intracortical application of GHB induced epileptogenic spikes (< 0.5 Hz) behaviorally accompanied by occasional myoclonic jerks and epileptic discharges (< 2 Hz) with behavioral convulsions and contraversive movements towards the left hindlimb (seizures) but did not induce HVS or spike and waves, as reported after systemic application. In the group of rats with spontaneous occurring HVS the amplitude of the HVS on the side of the microdialysis probe was suppressed by GHB and GHB-induced spikes invading the contralateral cortex frequently triggered and terminated local HVS. The results point to different neural mechanisms for the generation of HVS and spikes and epileptic discharges (seizures) induced after local intracortical application of GHB.